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Trial to Evaluate the Interest of a Reductive Anti Retroviral Strategy Using Dual Therapy Inspite of Triple Therapy (TRULIGHT)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02302547
First Posted: November 27, 2014
Last Update Posted: October 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
HOSPITAL, ORLEANS
Poitiers University Hospital
Centre Hospitalier de La Rochelle
HOSPITAL, SAINTES
HOSPITAL, FOCH
HOSPITAL, CAEN
HOSPITAL, HENRI MONDOR
HOSPITAL, HOTEL DIEU
HOSPITAL, CHARTRES
HOSPITAL, SAINT LOUIS
Tourcoing Hospital
HOSPITAL, NIORT
Tenon Hospital, Paris
Central Hospital, Nancy, France
University Hospital, Rouen
Information provided by (Responsible Party):
University Hospital, Tours
  Purpose

In the early 2000s, the "TRILEGE©" study was realized to determine if the reductive anti retroviral strategy from an initial triple therapy (based on a protease inhibitor as the third agent) towards a dual therapy of nucleoside analogs (in particular the association of "zidovudine +lamivudine") for patients infected by HIV and stabilized for at least 3 months at a threshold value of 400 copies/ml, would allow to obtain a well-controlled plasmatic viral load, with an aim to reduce the long-term side effects of the treatment.

The afore mentioned study showed that the reductive anti retroviral strategy was a failure. No study has as yet to revaluate this strategy, in particular in the current context of antiretroviral treatments.

Indeed, modern nucleoside inhibitors (Kivexa®, Truvada®) have extended half-lives as well as a superior intrinsic power as compared to treatments proposed in the initial "TRILEGE©" study. Furthermore, the better quality of current triple therapy (as compared to that used 10 years ago) has lead to substantial viral reservoir reduction.

Currently, a small number of patients is being successfully treated in the long-term (viral load < 20 copies/ml) using nucleoside analog dual therapy. The particular characteristics of these patients have yet to be thoroughly investigated.

The patients concerned were all treated prematurely before ever passing below 200 lymphocytes T CD4/mm3. It occurred that all these patients presented a low viral reservoir as measured by HIV DNA quantification (< 2,7 log copies/106 PBMC).

Therefore, by targeting patients who have (1) a strong immune restoration, (2) a low HIV DNA value and (3) a very good observance, the investigators emit the hypothesis that, reductive anti retroviral strategy that would consist in changing from a conventional triple therapy towards a Nucleoside reverse-transcriptase inhibitors dual therapy, could allow for durable control of viral replication with the concomitant benefice of reduced antiretroviral side effects and cost.


Condition Intervention Phase
HIV Drug: triple therapy Drug: dual therapy Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Clinical Trial to Evaluate the Interest of a Down-scaled Treatment Strategy Using Dual Therapy (Nucleoside Analogs) in HIV Infected Patients Already Being Treated Using Triple Therapy, Who Present With a Successful Virological Control and for Which the HIV Reservoir is Low to Moderate

Resource links provided by NLM:


Further study details as provided by University Hospital, Tours:

Primary Outcome Measures:
  • Viral Load at 48 weeks [ Time Frame: 48 weeks ]
    Percentage of patient having a viral load < 50 copies/ml in each arm reductive anti retroviral strategy from an original backbone of 2 Nucleoside reverse transcriptase inhibitors (Tenofovir Disoproxil Fumarate+ Emtricitabine) coupled to a third agent, towards a therapeutic strategy containing the backbone therapy alone (Truvada®).


Secondary Outcome Measures:
  • Change from week 4 in Viral load at 48 weeks [ Time Frame: between 4 weeks and 48 weeks ]
    percentage of patients having a viral load between 50 and 400 copies/ml between week 4 and week 48

  • CD 4 level in each arm [ Time Frame: 48 weeks ]
    delta CD 4 measurement in each arm

  • Change from day 0 in HIV - DNA at week 48 [ Time Frame: day 0 and 48 weeks ]
    HIV DNA evolution between day 0 and week 48 in each arm


Enrollment: 224
Actual Study Start Date: December 2014
Estimated Study Completion Date: August 2018
Primary Completion Date: August 23, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: triple therapy
Tenofovir Disoproxil Fumarate (nucleotide reverse transcriptase inhibitor) + Emtricitabine (nucleoside reverse transcriptase inhibitor) + third agent (boosted protease inhibitor or unboosted protease inhibitor or integrase inhibitor or celsentri or non-nucleoside reverse transcriptase inhibitor).
Drug: triple therapy
Dosage treatment and usual prescription
Other Names:
  • Tenofovir+Emtricitabine+Third agent (Including a non nucleoside reverse transcriptase inhibitor: efavirenz or nevirapine or etravirine or rilpivirine
  • Tenofovir+Emtricitabine+Third agent (Including a ritonavir-boosted protease inhibitor : saquinavir or indinavir or fosamprenavir or tipranavir or darunavir or atazanavir or lopinavir
  • Tenofovir+Emtricitabine+Third agent (Including an unboosted protease inhibitor: atazanavir or indinavir
  • Tenofovir+Emtricitabine+Third agent (Including an integrase inhibitor raltegravir or dolutegravir or cobicistat-boosted elvitegravir
  • Tenofovir+Emtricitabine+Third agent (Including a fusion inhibitor: enfuvirtide or a CCR5 antagonist :maraviroc
Experimental: dual therapy
Truvada®"245mg":oral administration Tenofovir Disoproxil Fumarate (nucleotide reverse transcriptase inhibitor) + Emtricitabine (nucleoside reverse transcriptase inhibitor)
Drug: dual therapy
1 tablet (200mg/245mg) daily for 48 weeks
Other Name: Truvada®

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infected patient
  • Initial TT ARV started above (or equal to) 150 / mm3 LT CD4, and 18 months prior to inclusion in the study
  • Ongoing antiretroviral therapy combining tenofovir + emtricitabine + a 3rd agent (IP / r, IP, NNRTI, II, Inhibitors) with at least one undetectable viral load (CV <50 copies / mL) after introduction of the latter treatment.
  • Patient in virological success: CV <50 copies / mL for at least 12 months, including visit to selection.
  • Absence of previous therapeutic failure: no viral load ≥ 200 copies / mL (after 6 months of treatment) (Except in the case of a justified therapeutic interruption: travel, stock-out ...) and of obtaining success Virologic after introduction of treatment, without concept of genotypic resistance known to the ARVs used.
  • Cellular DNA-HIV <2.7 log copies / 106 PBMC
  • Zenith RNA-HIV <150,000 copies / ml (excluding viral load values during primary infection if it is documented)
  • No genotypic resistance to currently used and known ARVs
  • Patient who has given written informed consent
  • Affiliate or beneficiary of a social security scheme
  • Patient followed on an outpatient basis, age ≥ 18 years.

Exclusion Criteria:

  • Non-compliant patient
  • Subject is pregnant, or lactating, or of childbearing potential and without contraception
  • Active opportunistic infections
  • Major overweight (BMI ≥ 40)
  • Severe renal pathology (creatinine clearance < 30ml/min)
  • Cirrhosis or severe liver failure (factor V < 50%)
  • Prognosis threatened within 6 months
  • Circumstances that may impair judgment or understanding of the information given to the patient
  • Malabsorption syndromes
  • The following laboratory criteria:

    • Serum ASAT,ALAT > 5 x upper limit of normal (ULN)
    • Thrombocytopenia with platelet count < 50.000/ml
    • Anemia with hemoglobin < 8g/dl
    • Polynuclear neutrophil count < 500/mm3
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02302547


Locations
France
Unité des Maladies Infectieuses, CHU de CAEN
Caen, France, 14033
Service des Maladies Infectieuses, CHR Orléans La Source, ORLEANS CEDEX 2
CHR d'ORLEANS, France, 45067
Service d'Immunologie Clinique centre de Vaccination anti- VIH ANRS Hopital Henri- Mondor
Creteil, France, 94010
Service de Médecine Interne et Maladies Infectieuses, Groupe Hospitalier La Rochelle, Cedex 01
La Rochelle, France, 17019
Service de Pneumologie, centre Hospitalier Fontenoy, CH de CHARTRES
Le Coudray, France, 28630
CHU de NANCY
Nancy, France, 54035
Service des maladies Infectieuses et tropicales, CH GEORGES RENON
Niort, France, 79021
Service des Maladies Infectieuses et tropicales, APHP SAINT LOUIS
Paris, France, 75475
Hospital Tenon
Paris, France, 75970
Centre de diagnostic et thérapeutique, Hopital Hotel Dieu
Paris, France, 94010
Consultation Maladies Infectieuses, Chu de Poitiers, Cedex
Poitiers, France, 86021
Maladies Infectieuses, CHU de ROUEN
Rouen, France, 76031
Service de Médecine Interne, CH de SAINTONGE- BP 326
Saintes, France, 17108
Médecine Interne, Hôpital FOCH
Suresnes, France, 92151
Service Universitaire des Maladies Infectieuses et du Voyageur, CH DRON
Tourcoing, France, 59200
Service de Medecine Interne et Maladies Infectieuses, CHRU BRETONNEAU, TOURS CEDEX9
Tours, France, 37044
Sponsors and Collaborators
University Hospital, Tours
HOSPITAL, ORLEANS
Poitiers University Hospital
Centre Hospitalier de La Rochelle
HOSPITAL, SAINTES
HOSPITAL, FOCH
HOSPITAL, CAEN
HOSPITAL, HENRI MONDOR
HOSPITAL, HOTEL DIEU
HOSPITAL, CHARTRES
HOSPITAL, SAINT LOUIS
Tourcoing Hospital
HOSPITAL, NIORT
Tenon Hospital, Paris
Central Hospital, Nancy, France
University Hospital, Rouen
Investigators
Principal Investigator: LOUIS BERNARD, Pr CHRU de TOURS
Principal Investigator: GWENAEL LE MOAL, Dr Poitiers University Hospital
Principal Investigator: MARIAM RONCATO- SABERAN, Dr CH de LA ROCHELLE
Principal Investigator: THIERRY PASDELOUPS, Dr CH de SAINTES
Principal Investigator: DAVID ZUCMAN, Dr HOPITAL de FOCH
Principal Investigator: RENAUD VERDON, Pr University Hospital, Caen
Principal Investigator: SEBASTIEN GALLIEN, Pr CHU d'HENRI MONDOR
Principal Investigator: JEAN - PAUL VIARD, Pr CH d'HOTEL DIEU
Principal Investigator: MARC LESTELLE, Dr CH de CHARTRES
Principal Investigator: JEAN - MICHEL MOLINA, Pr CHU SAINT LOUIS
Principal Investigator: FAÏZA AJANA, Dr CH de TOURCOING
Principal Investigator: SIMON SUNDER, Dr CH de NIORT
Principal Investigator: Gilles PIALOUX, Pr HOSPITAL TENON
Principal Investigator: Thierry MAY, Dr CHU de Nancy
Principal Investigator: Manuel ETIENNE, Dr CHU de ROUEN
  More Information

Responsible Party: University Hospital, Tours
ClinicalTrials.gov Identifier: NCT02302547     History of Changes
Other Study ID Numbers: PHAO13-TP/TRULIGHT
First Submitted: October 14, 2014
First Posted: November 27, 2014
Last Update Posted: October 6, 2017
Last Verified: October 2017

Keywords provided by University Hospital, Tours:
HIV-DNA
dual therapy
NRTI
virological control
truvada®

Additional relevant MeSH terms:
Tenofovir
Emtricitabine
Atazanavir Sulfate
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Dolutegravir
Indinavir
Fosamprenavir
Reverse Transcriptase Inhibitors
HIV Protease Inhibitors
Protease Inhibitors
Integrase Inhibitors
Antiviral Agents
Anti-Infective Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
HIV Integrase Inhibitors